# Potentiate Cav3.3 To Treat Cognitive Deficits Associated with Impaired Sleep Spindle

> **NIH NIH R01** · BROAD INSTITUTE, INC. · 2022 · $716,980

## Abstract

Project Summary/Abstract
Sleep spindle is a hallmark brain oscillation occurring in NREM (non-rapid eye movement) sleep that reflect
intrinsic thalamocortical offline processing. Spindles are waxing and waning bursts of 12-15 Hz oscillations
that originate in Thalamic Reticular Nucleus (TRN) when its neurons undergo bursting firing, and TRN-
Thalamic Relay network oscillates at spindle frequency through the reciprocal connection. Sleep spindles are
markedly reduced in schizophrenia patients as well as in Alzheimer patients, two very different CNS disorders
yet both demonstrated significant altered sleep spindle properties associated with cognitive impairment. We
hypothesize that hypofunctional TRN may underlie the risk/symptoms of these two devasting illnesses.
CACNA1I is encode the α1 functional core of the CaV3.3 voltage-ˇgated calcium channels, and its expression
is enriched in TRN. We have discovered two novel chemical scaffolds that potentiate CaV3.3 function, and this
proposal aims to deliver in vivo ready Cav3.3 positive modulators. This multidisciplinary effort is expected to
yield a panel of incisive pharmacological reagents to enhance CaV3.3 function in the brain and nominate
candidates for preclinical development for treating cognitive impairments in schizophrenia patients.

## Key facts

- **NIH application ID:** 10566385
- **Project number:** 1R01MH131719-01
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Jen Qian Pan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $716,980
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10566385

## Citation

> US National Institutes of Health, RePORTER application 10566385, Potentiate Cav3.3 To Treat Cognitive Deficits Associated with Impaired Sleep Spindle (1R01MH131719-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10566385. Licensed CC0.

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